Abstract The health literacy level among the elderly in China remains at a low level. The 14th Five-Year Plan for Healthy Aging clearly points out that health literacy promotion projects should be implemented to improve the health literacy level among the elderly. The health literacy promotion strategies for the elderly require individual, social, policy and environmental supports. This article reviewed four types of health literacy promotion strategies for the elderly, including social strategies, lecture-based health education strategies, new media-based health communication strategies and environmental strategies. It also proposed that health education institutions, communities and other parties should work together, take advantage of digital technology and internet, and take various measures simultaneously to improve the health literacy of the elderly.

Objective : To investigate the mechanism of puerarin in the treatment of rheumatoid arthritis(RA) by network pharmacology and animal experiments. Methods : Traditional Chinese Medicine Systems Pharmcolog Database(TCMSP) and SwissTargetPrediction database were used to collect puerarin targets, and the targets of RA were obtained from GeneCards database and OMIM database. The PPI network was established by Cytoscape 3.7.2 software. Gene ontology(GO) function and Kyotoencyclopedia of genes(KEGG) enrichment analysis were performed through the Metascape database. RA rat-collagen-induced arthritis(CIA) model was reproduced using type Ⅱ collagen emulsion, 49 Wistar rats were randomly assigned to seven groups: control group, CIA model group, low-dose, medium-dose and high-dose puerarin group, methotrexate group, Tripterysium Glycosides Tablets group. Except for the control group, the other groups were given continuous gavage for 28 days after the CIA in rats model were prepared. The redness and swelling of the joints and ankle joint pathological changes were observed in each group. Western blot was used to detect the expression of Glycogen synthase kinase3β(GSK-3β), beta-catenin(β-catenin) proteins in the synovium. Real-time quantitative polymerase chain reaction(qPCR) was used to detect the expression of GSK-3β, β-catenin and c-Myc mRNA in the synovium. Results : Puerarin had 134 targets genes, RA had 5 821 target genes, and there were 102 overlapping target genes of puerarin and RA. It involved 184 signaling pathways, including JAK-STAT signaling pathway, NF-κB signaling pathway, Wnt signaling pathway, et al. The results of animal experiments showed that after the intervention of M-puerarin and MTX, the symptoms of redness and swelling of the hind foot were alleviated, the inflammatory cell infiltration in the synovium of the joint was significantly reduced, and the damage of cartilage and bone tissue was reduced. Compared with CIA group, the expressions of GSK-3β, β-catenin protein and GSK-3β, β-catenin and c-Myc mRNA in synovial tissue of rats after M-puerarin intervention decreased(P<0.05). Conclusion Puerarin has the characteristic of multi-components, multi-targets and multi-pathway intervention in RA. Puerarin may alleviate synovial hyperplasia, reduce articular cartilage erosion and bone destruction in CIA in rats by inhibiting Wnt/β-catenin signaling pathway.

Background At present, the treatment of silicosis is still limited, and no method is available to cure the disease. miRNAs are involved in the process of fibrosis at the transcriptional level by directly degrading target gene mRNA or inhibiting its translation. However, how miR-130a-3p regulates silicosis fibrosis has not been fully elucidated yet. Objective To investigate whether miR-130a-3p promotes epithelial-mesenchymal transition (EMT) by inhibiting peroxisome proliferators-activated receptors gamma (PPAR-γ), thereby pro-moting the process of silicotic fibrosis. To identify effective new targets for the treatment of silicotic fibrosis. Methods (1) Animal experiments: C57BL/6J mice were intratracheally injected with a one-time dose of 10 mg silica suspension (dissolved in 100 μL saline) as positive lung exposure. A silicosis model group was established 28 d after the exposure. A control group was injected with the same amount of normal saline into the trachea. Hematoxylin-eosin staining and Sirius red staining were used to observe the pathological changes and collagen deposition in lung tissues respectively. Realtime fluorescence-based quantitative polymerase chain reaction (RT-qPCR) was used to assay the expression of miR-130a-3p and PPAR-γ mRNA in lung tissues. Western blotting was used to detect the protein expression of PPAR-γ, transforming growth factor (TGF)-β1, E-cadherin, α-smooth muscle actin (α-SMA), and Collagen Ⅰ in lung tissues. (2) Cells experiments: Mouse lung epithelial cells (MLE-12) were induced with 5 µg·L⁻¹ TGF-β1 for different time (0, 12, 24, 48 h). RT-qPCR was used to detect the expression of miR-130a-3p and PPAR-γ mRNA in cells. The binding relationship between miR-130a-3p and PPAR-γ mRNA was verified by dual luciferase reporter gene assay. MLE-12 cells were stimulated by 5 µg·L⁻¹ TGF-β1 after transfection of miR-130a-3p inhibitor, and Western blotting was used to measure the protein expression of PPAR-γ, E-cadherin, and α-SMA in the TGF-β1-induced cells. Results In the silicosis model group, the alveolar septum was widened and the pulmonary nodules were formed. The Sirius red staining collagen deposition in pulmonary nodules indicated that a silicosis fibrosis model was successfully established. The expressions of TGF-β1, α-SMA, and Collagen Ⅰ proteins were increased, and the expressions of E-cadherin and PPAR-γ proteins were decreased in lung tissues of the silicosis group, compared with the control group (P<0.05 or P<0.01). The expression of miR-130a-3p was increased and the expression of PPAR-γ mRNA was decreased in lung tissues of the silicosis model (P<0.01). The expression of miR-130a-3p was significantly increased, while the expression of PPAR-γ mRNA was decreased in the TGF-β1 induced MLE-12 cells (P<0.05 or P<0.01). The dual luciferase reporter assay showed a direct relationship between miR-130a-3p and PPAR-γ mRNA in MLE-12 cells. The transfection of miR-130a-3p inhibitor in the TGF-β1 induced MLE-12 cells inhibited the decrease of PPAR-γ and E-cadherin proteins, and the increase of α-SMA protein in the MLE-12 cells induced by TGF-β1 (P<0.05 or P<0.01). Conclusion miR-130a-3p promotes the development of silicosis fibrosis by targeting PPAR-γ to increase pulmonary EMT.

With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

ObjectiveTo elucidate the correlation between alterations in digestion and absorption functions and hepatic deficiency states in aging rats based on the R-spondin1/Wnt3a signaling pathway， and reveal the intervention mechanism of Bugansan. MethodsForty-eight SPF-grade male SD rats were randomly assigned to six groups： blank control， model， low-， medium-， and high-dose （7.03， 14.06， 28.12 g·kg^-1， respectively） Bugansan， and vitamin E （suspension， 27 mg·kg^-1）， with 8 rats in each group. The rat model of aging was established by intraperitoneal injection of D-galactose （400 mg·kg^-1）， while the blank control group was injected with normal saline. Since the day of modeling， rats in intervention groups received corresponding agents by gavage， and those in blank control and model groups received an equal volume of normal saline （10 mL·kg^-1）. General biological features such as fur color， activity， body mass， water intake， and food intake were observed. Meanwhile， the content of malondialdehyde （MDA） and the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in the serum were measured to assess aging. Grip strength and the content of total bile acids （TBA） and the activity of α-amylase （AMY） in the serum were measured to evaluate hepatic deficiency states. The activity of β-galactosidase （β-gal） in the duodenum was measured to evaluate intestinal senescence. The levels of glucagon-like peptide-1 （GLP-1）， vasoactive intestinal peptide （VIP）， and D-xylose in the serum were determined to assess digestion and absorption functions of the small intestine. Hematoxylin-eosin staining was conducted to observe pathological changes of the duodenum to assess the small intestine damage. Immunohistochemical staining was employed to visualize the expression of B-cell-specific Moloney murine leukemia virus integration site 1 （Bmi1） and leucine-rich repeat-containing G protein-coupled receptor 5 （Lgr5） in the duodenal tissue. Moreover， Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to quantify the mRNA levels of Ki67， Bmi1， and Lgr5 to assess proliferation and regeneration of the small intestine. Additionally， the mRNA levels of R-spondin1， Wnt3a， β-catenin， and glycogen synthase kinase-3β （GSK-3β） and the protein levels of R-spondin1， Wnt3a， β-catenin， and phosphorylated GSK-3β （p-GSK-3β） in the duodenum were determined by Real-time PCR and Western blot， respectively， to analyze the mechanisms of intestinal digestion and absorption dysfunction in aging rats and the regulatory characteristics of Bugansan. ResultsCompared with blank control group， the model group showed decreases in body mass， water intake， food intake， grip strength， activities of SOD， GSH-Px， and AMY in the serum and content of GLP-1， VIP and D-xylose in the serum （P<0.05）， increases in the content of MDA and TBA in the serum and β-gal activity in the duodenum （P<0.05）， reductions in villus length， villus width， crypt depth， and villi/crypt （V/C） value， down-regulated mRNA and protein levels of Ki67， Lgr5， Bmi1， R-spondin1， Wnt3a， β-catenin， and up-regulated level of GSK-3β， phosphorylation （p）-GSK-3β （P<0.05）. Compared with the model group， Bugansan increased the body mass， water intake， food intake， grip strength， and activities of SOD， GSH-Px， and AMY and levels of GLP-1， VIP and D-xylose in the serum （P<0.05）， while decreasing the content of MDA and TBA in the serum and β-gal activity in the duodenum （P<0.05）. Furthermore， Bugansan increased the villus length， villus width， crypt depth， and V/C value， up-regulated the mRNA and protein levels of Ki67， Lgr5， Bmi1， R-spondin1， Wnt3a， β-catenin， and down-regulated the level of GSK-3β and p-GSK-3β （P<0.05）. ConclusionAging rats exhibit obvious impairments in digestion and absorption functions， accompanied by a state of hepatic deficiency. The traditional Chinese medicine approach of tonifying liver Qi effectively ameliorates aging-related changes by modulating the R-spondin1/Wnt3a signaling pathway to mitigate intestinal senescence and enhance digestion and absorption functions， ultimately contributing to the delay of aging.

ObjectiveThis study sought to investigate the impact of exosomes derived from LoVo cells (LoVo-Exos) in colorectal cancer (CRC) on tumor angiogenesis, as well as to elucidate the potential molecular mechanisms underlying their pro-angiogenic effects. MethodsLoVo-Exos were isolated via ultracentrifugation, and their internalization into recipient human umbilical vein endothelial cells (HUVECs) was visualized using confocal microscopy. The influence of LoVo-Exos on angiogenesis was assessed through an in vitro tube formation assay. Additionally, the pro-angiogenic effects of LoVo-Exos were evaluated in vivo using a matrix gluing assay in mice. To investigate the molecular mechanisms through which LoVo-Exos facilitate angiogenesis, Western blot analysis was employed to examine the transfer of pEGFR by LoVo-Exos into recipient cells. Both Western blot and ELISA were utilized to assess the expression levels of key signaling proteins within the EGFR-ERK pathway, as well as the expression of downstream angiogenic core molecules. Furthermore, the impact of EGFR knockdown and ERK inhibitor treatment on angiogenesis was evaluated, with subsequent analysis of the expression of downstream angiogenic core molecules following these interventions. ResultsConfocal microscopy demonstrated the internalization of LoVo-Exos into HUVECs. In vitro angiogenesis assays further indicated that LoVo-Exos significantly enhanced the formation of tubular structures in HUVECs. Additionally, macroscopic examination of subcutaneous matrix plug formation in mice revealed a substantial increase in vascular-like structures within the matrix plugs following the administration of LoVo-Exos, compared to the PBS control group. Hematoxylin and eosin (HE) staining revealed the presence of erythrocyte-filled microvessels within the matrix plugs combined with LoVo-Exos. Furthermore, immunohistochemical analysis demonstrated the expression of the endothelial cell marker CD31 in these matrix plugs. The presence of CD31-positive cells in the LoVo-Exos-treated matrix plugs was associated with a significant enhancement in the formation of luminal structures. These findings suggest that LoVo-Exos facilitate the in vivo development of vascular-like structures. Subsequent investigations demonstrated that LoVo-Exos facilitated the delivery of pEGFR to HUVEC, thereby enhancing angiogenesis. Conversely, LoVo-Exos with EGFR knockdown exhibited a diminished capacity to promote angiogenesis, an effect that was further attenuated by the ERK phosphorylation inhibitor U0126. Western blot analysis assessing the activation of the EGFR-ERK signaling pathway in HUVEC indicated that LoVo-Exos augmented angiogenesis through the activation of this pathway. Furthermore, analysis of the impact of LoVo-Exos on the expression of downstream angiogenic core molecules revealed an increase in interleukin-8 (IL-8) secretion in HUVEC. The enhancement observed was diminished in LoVo-Exos following EGFR knockdown, and this reduction was counteracted by the ERK phosphorylation inhibitor U0126. ConclusionThe underlying mechanism may involve the delivery of pEGFR in LoVo-Exos to HUVECs, leading to increased IL-8 secretion via the EGFR-ERK signaling pathway, thereby enhancing the angiogenic potential of HUVECs. This finding may offer new insights into the mechanisms underlying cancer metastasis.

BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.

This study aims to investigate the ameliorating effect of Corni Fructus(CF) on the myocardial ischemic injury and the pharmacokinetic properties of characteristic components of CF. The mouse model of isoproterenol-induced myocardial ischemia was established and administrated with the aqueous extract of CF. The general efficacy of CF in ameliorating the myocardial ischemic injury was evaluated based on the cardiac histopathology and the levels of myocardial injury markers: creatine kinase isoenzyme(CK-MB) and cardiac troponin I(cTn-I). The metabolomics analysis was carried out for the heart and serum samples of mice to screen the biomarkers of CF in ameliorating the myocardial ischemic injury and then the predicted biomarkers were submitted to metabolic pathway enrichment. The pharmacokinetic analysis was performed for morroniside, loganin, and cornuside Ⅰ in mouse heart and serum samples to obtain the pharmacokinetic parameters of these components. The pharmacokinetic parameters were then integrated on the basis of self-defined weighting coefficients to simulate an integrated pharmacokinetic profile of CF iridoid glycosides in the heart and serum of the mouse model of myocardial ischemia. The results indicated that CF reduced the pathological damage to cardiac cells and tissue(hematoxylin-eosin staining) and lowered the levels of CK-MB and cTn-I in the serum of the mouse model of myocardial ischemia(P<0.01). Metabolomics analysis screed out 31 endogenous metabolites in the heart and 35 in the serum as biomarkers of CF in ameliorating the myocardial ischemic injury. These biomarkers were altered by modeling and restored by CF. Six metabolic pathways in the heart and 5 in the serum were enriched based on these metabolic markers. The main integrated pharmacokinetic parameters of CF iridoid glycosides were T_(max)=1 h, t_(1/2)=(1.52±0.05) h in the heart and T_(max)=1 h, t_(1/2)=(1.56±0.50) h in the serum. Both concentration-time curves showed a double-peak phenomenon. In conclusion, CF demonstrated the cardioprotective effect by regulating metabolic pathways such as taurine and hypotaurine metabolism, and pantothenic acid and coenzyme A biosynthesis. The integrated pharmacokinetics reflect the general pharmacokinetic properties of characteristic components in CF.
Animals ; Cornus/chemistry* ; Mice ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Myocardial Ischemia/metabolism* ; Humans ; Troponin I/metabolism* ; Myocardium/pathology* ; Disease Models, Animal ; Biomarkers/metabolism* ; Creatine Kinase, MB Form/metabolism*

Callicarpa is an important medicinal plant in China, which has hemostatic, antibacterial, and antioxidant pharmacological effects, and the efficacy of astringing and arresting bleeding, clearing heat and detoxification, activating blood, and resolving stasis is outstanding. At the same time, Callicarpa can be used as an ornamental plant because of its gorgeous flowers and fruits. Callicarpa has good market development prospects, but the long seed reproduction cycle directly limits the large demand for seedlings in its industrial development. Asexual reproduction technology is the basis for the industrialization development of Callicarpa, which is helpful in producing high-quality seedlings and medicinal materials. Although Chinese and foreign scholars have achieved remarkable results in the study of asexual reproduction of Callicarpa, there is no report on the large-scale production of seedlings of Callicarpa. Integrating and improving its asexual reproduction technology can promote the development and utilization of Callicarpa, improve its medicinal value, and create significant economic benefits. Therefore, the authors reviewed the effects of cutting, season, plant growth regulators, substrates, environment, and management measures on the cutting of Callicarpa and the research progress of tissue culture propagation affected by explants, basic media, exogenous additives, subculture cycles, culture conditions, and transplanting substrates. The mechanism of adventitious root formation was reviewed at the cellular, physiological, and biochemical levels, so as to put forward the problems and corresponding solutions in the study of asexual propagation technology and regulatory mechanism of Callicarpa and point out the future research directions. The study aims to provide a reference for in-depth research on the asexual propagation technology of Callicarpa and the commercial production of its high-quality seedlings.
Reproduction, Asexual ; Plants, Medicinal/physiology* ; Seedlings/growth & development* ; Tissue Culture Techniques

This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China